Cell cycle regulation is essential to the development of an organism. The complexity of embryogenesis requires a precise program of control and a wide array of important proteins. Regulation of the cell cycle during development is critical for patterns of proliferation that determine the size or shape of a tissue, as well as for the decision of cells to withdraw from the cell cycle in order to differentiate. There is new evidence revealing that developmental patterning signals feed into cell cycle machinery. We are interested in analyzing a very important step in the cell cycle, the G1-S transition, and its associated proteins. This is the time when a cell must decide whether to terminally differentiate or continue to proliferate. Positive and negative regulators of this transition affect the activity of the E2F/DP family of transcription factors. The long term goal of this project is establish a link between cell signaling pathways and regulation of the G1-S transition, using Drosophila melanogaster as a model system. The specific aims of the proposal are: 1) Genetic identification of mutations in novel genes that act to regulate dE2F/dDP function by performing a genetic modifier screen for dominant suppressors of dDPa1 induced sterility; 2) Phenotypic characterization and cloning of novel mutations affecting dE2F/dDp function that result from the screen; and 3) Analysis of the effects cell signaling pathways have on the regulation of the cell cycle in the developing midgut. The G1-S transition is important for control of proliferation. Therefore it is not surprising that some cancerous cells have been shown to have mutations in genes that regulate this transition. It is thus our hope that analysis of dE2F/dDp activity will lead us to a greater understanding of the mechanism of the onset of cancer.